Microspheres and method for producing them

Abstract

Provided is an organic solvent-free method for producing a plurality of microsphere having an average diameter of less than 500 μm in diameter and having average contact angle θc greater than 140°, consisting essentially of a biocompatible hot-melt carrier vehicle and a payload substance to be delivered, including melting and mixing a polymer carrier vehicle which is solid at room temperature and at least one payload substance, and dispensing microportions of the molten mixture through a droplet-forming space onto a cooled solid superoleophobic surface.

What is claimed is: 
     
       1. A method for producing a plurality of microsphere having an average diameter of less than 500 μm in diameter and an average contact angle θc greater than 140°, the method comprising:
 heating and mixing a polymeric carrier vehicle with at least one payload substance to obtain a molten mixture free of organic solvent; dispensing microportions of the molten mixture through an orifice of a droplet-forming space onto a solid superoleophobic surface; and 
 allowing the dispensed microportions to stabilize on the superoleophobic surface, 
 wherein said polymeric carrier vehicle is biocompatible and has a melting point of about 45° C. to 200° C.; 
 wherein the payload has a melting point suitable to be dissolved or dispersed in the molten mixture; 
 wherein the payload has thermal stability in the molten mixture; 
 wherein the payload is solid or liquid at room temperature; 
 wherein said molten mixture has a viscosity between about 100 mPas and about 2,500 mPas; 
 wherein stabilization of the microportions is within a time period of a fraction of a second, whereby said plurality of microspheres are formed. 
 
     
     
       2. The method of  claim 1 , wherein said polymeric carrier vehicle is heated to form a hot-melt carrier and subsequently mixed with the at least one payload substance into a molten dispersion or solution. 
     
     
       3. The method of  claim 1 , wherein said polymeric carrier vehicle is mixed with the at least one payload substance and subsequently heated into a molten dispersion or solution. 
     
     
       4. The method of  claim 1 , wherein said polymeric carrier comprises poly(lactic-co-glycolic acid) (PLGA) and said payload comprises essential oil. 
     
     
       5. The method of  claim 1 , comprising dispensing said molten mixture through said droplet-forming space having a nozzle orifice size of between 50 μm-150 μm. 
     
     
       6. The method of  claim 1 , wherein the superoleophobic surface is at room temperature. 
     
     
       7. The method of  claim 1 , wherein the superoleophobic surface is maintained at a temperature below 0° C. 
     
     
       8. The method of  claim 1 , wherein said microdroplets are formed by any one of (i) pushing, (ii) applying pulsatile pressure, and (iii) applying constant pressure and cycling between opening and closing an extrusion valve on the molten mixture when the molten mixture is dispensed through said orifice. 
     
     
       9. The method of  claim 1 , wherein the drop-forming space is a vacuum or filled with one or more gases selected from the group consisting of air, nitrogen, argon, and xenon. 
     
     
       10. The method of  claim 1 , wherein each microsphere within the plurality of microspheres comprise a mixture of polymeric carrier vehicle and a payload substance;
 at least 75% of the plurality of microspheres having a uniform spherical surface; 
 at least 75% of the plurality of microspheres have a contact angle θc greater than 140°. 
 
     
     
       11. The method of  claim 1  wherein a thermal barrier is suspended in the droplet forming space above the superoleophobic surface, at a height at least 100 μm greater than the average diameter of the microspheres. 
     
     
       12. The method of  claim 1 , wherein the polymeric carrier vehicle comprise a member selected from the group consisting of polylactic acid, Poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), cetyl alcohol, oxidized polyethylene (PE), and waxes. 
     
     
       13. The method of  claim 1 , wherein the payload substance comprises oil. 
     
     
       14. The method of  claim 1 , wherein said microportions of molten mixture are dispensed through said droplet-forming space with a distance between an ejection nozzle and the superoleophobic surface sufficiently short to allow the molten mixture to reach the superoleophobic surface in a molten state. 
     
     
       15. The method of  claim 14 , wherein the distance between the ejection nozzle and the superoleophobic surface is less than 4 mm. 
     
     
       16. The method of  claim 14 , wherein the drop-forming space between the ejection nozzle and the superoleophobic surface is less than 2 mm.